KH 1060 - A NEW VITAMIN D ANALOGUE WITH POTENT EFFECTS ON CELL-MEDIATED IMMUNE RESPONSES IN VITRO

Vitamin D ◽  
1991 ◽  
pp. 516-517 ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 391-393 ◽  
Author(s):  
Hanne Sørensen ◽  
Lise Blnderup ◽  
Martin J. Calverley ◽  
Lene Hoffmeyer ◽  
Niels Rastrup Andersen

1995 ◽  
Vol 310 (1) ◽  
pp. 233-241 ◽  
Author(s):  
S Strugnell ◽  
V Byford ◽  
H L J Makin ◽  
R M Moriarty ◽  
R Gilardi ◽  
...  

A major metabolite of the vitamin D analogue 1 alpha-hydroxyvitamin D2 in human liver cells in culture has been identified as 1 alpha,24(S)-dihydroxyvitamin D2 [1 alpha,24(S)-(OH)2D2]. 1 alpha-Hydroxyvitamin D3 incubated with the same cells gives rise to predominantly 25- and 27-hydroxylated products. Our identification of 1 alpha,24(S)-dihydroxyvitamin D2 is based on comparisons of the liver cell metabolite with chemically synthesized 1 alpha,24(S)-(OH)2D2 and 1 alpha,24(R)-(OH)2D2 by using HPLC, GC and GC-MS techniques. The stereochemical orientation of the 24-hydroxyl group was inferred after X-ray-crystallographic analysis of the 24(R)-OH epimer. 1 alpha,24(S)-Dihydroxyvitamin D2 binds strongly to the vitamin D receptor and is biologically active in growth hormone and chloramphenicol acetyltransferase reporter gene expression systems in vitro, but binds poorly to rat vitamin D-binding globulin, DBP. We suggest that this metabolite, 1 alpha,24(S)-(OH)2D2, possesses the spectrum of biological properties to be useful as a drug in the treatment of psoriasis, metabolic bone disease and cancer.


1992 ◽  
Vol 44 (12) ◽  
pp. 2273-2280 ◽  
Author(s):  
Kay W. Colston ◽  
Alan G. Mackay ◽  
Sharon Y. James ◽  
Lise Binderup ◽  
Surinder Chander ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 276
Author(s):  
Amy S. Bleakley ◽  
Paul V. Licciardi ◽  
Michael J. Binks

Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are Streptococcus pneumoniae, respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms “vitamin D” and “Streptococcus pneumoniae” or “Respiratory Syncytial Virus” or “Influenza”. A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.


1994 ◽  
Vol 141 (3) ◽  
pp. 555-563 ◽  
Author(s):  
S Y James ◽  
A G Mackay ◽  
L Binderup ◽  
K W Colston

Abstract The anti-proliferative effects of the novel vitamin D analogue, EB1089, were assessed in the hormone-dependent breast cancer cell line, MCF-7, in vitro. In the present study, EB1089 was shown to be at least an order of magnitude more potent at inhibiting MCF-7 cell proliferation than the native hormone, lα,25-dihydroxyvitamin D3 (1,25(OH)2D3). Treatment of MCF-7 cell cultures with combinations of oestradiol and EB1089 ranging from 5 × 10−11 m to 5 × 10−9 m revealed the ability of EB1089 to suppress the mitogenic effects of oestradiol in these cells dose-dependently, as determined by [3H]thymidine incorporation and cell counts. EB1089 also exhibited a significant time- and dose-dependent decrease in MCF-7 oestrogen receptor (ER) concentration, as assessed by ligand binding assay. A fourfold reduction of ER levels by 5 × 10−9 m EB1089 relative to control ER levels was observed, whilst 5 × 10−9 m 1,25(OH)2D3 produced a significant but less dramatic decrease in ER levels. In addition, reduction of ER protein in EB1089-treated cell cultures was also demonstrated using an oestrogen receptor enzyme immunoassay. The interaction of EB1089 and anti-oestrogens on the oestradiol-stimulated growth of MCF-7 cells was investigated. The treatment of cell cultures with 5 × 10−10 m EB1089 in combination with the pure anti-oestrogen, ICI 182,780 (5 × 10−8 m), and in the presence of between 5 × 10−10 m and 5 × 10−9 m oestradiol, produced an augmented inhibition of MCF-7 cell proliferation compared with the actions of either compound alone. This study demonstrates that EB1089 is a potent anti-proliferative agent of breast cancer cells in vitro, and that part of its mechanism to inhibit cell growth may involve the modulation of ER expression, such that the responsiveness of cells to the growth-stimulatory effects of oestradiol is diminished. This new vitamin D analogue has potential in the treatment of breast cancer. Journal of Endocrinology (1994) 141, 555–563


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Mahgol Taghivand ◽  
Lisa G. Pell ◽  
Mohammed Z. Rahman ◽  
Abdullah A. Mahmud ◽  
Eric O. Ohuma ◽  
...  

Abstract Background Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. Methods This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. Results Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). Conclusion Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.


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